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Journal articles on the topic 'Adenovirus diseases'
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1
Watanabe, Maki, Yuya Nishikawaji, Hirotaka Kawakami, and Ken-ichiro Kosai. "Adenovirus Biology, Recombinant Adenovirus, and Adenovirus Usage in Gene Therapy." Viruses 13, no. 12 (December 14, 2021): 2502. http://dx.doi.org/10.3390/v13122502.
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Gene therapy is currently in the public spotlight. Several gene therapy products, including oncolytic virus (OV), which predominantly replicates in and kills cancer cells, and COVID-19 vaccines have recently been commercialized. Recombinant adenoviruses, including replication-defective adenoviral vector and conditionally replicating adenovirus (CRA; oncolytic adenovirus), have been extensively studied and used in clinical trials for cancer and vaccines. Here, we review the biology of wild-type adenoviruses, the methodological principle for constructing recombinant adenoviruses, therapeutic applications of recombinant adenoviruses, and new technologies in pluripotent stem cell (PSC)-based regenerative medicine. Moreover, this article describes the technology platform for efficient construction of diverse “CRAs that can specifically target tumors with multiple factors” (m-CRAs). This technology allows for modification of four parts in the adenoviral E1 region and the subsequent insertion of a therapeutic gene and promoter to enhance cancer-specific viral replication (i.e., safety) as well as therapeutic effects. The screening study using the m-CRA technology successfully identified survivin-responsive m-CRA (Surv.m-CRA) as among the best m-CRAs, and clinical trials of Surv.m-CRA are underway for patients with cancer. This article also describes new recombinant adenovirus-based technologies for solving issues in PSC-based regenerative medicine.
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Ageeva, M. R., and S. B. Yatsyshina. "UNDERESTIMATED INFECTION - ON THE QUESTION OF THE HUMAN ADENOVIRUS PATHOGENICITY FACTORS." Problems of Virology, Russian journal 64, no. 2 (April 20, 2019): 53–62. http://dx.doi.org/10.18821/0507-4088-2019-64-2-53-62.
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Human adenoviruses cause different organ infections of varying severity, from asymptomatic to severe cases with lethal outcome, that are registered everywhere. Detailed and focused study of factors predisposing to a severe course of infection is required. The literature contains information indicating the association of severe adenoviral respiratory diseases with certain types of adenovirus, primarily type 7. This review highlights the possible causes of increased pathogenicity of some types of adenovirus and their association with severe forms of infection. Pathogenicity factors include the ability of adenovirus to bind the specific cellular receptors, the formation of subviral particles, the interaction with blood proteins, in particular the coagulation factor X, as well as the features of the early genes E1A, E1B, E3, E4. In addition, the severity of the disease may be affected by the presence or absence of pre-existing antibodies specific to certain types of adenoviruses. Chronic diseases or immunosuppression also increase the risk of severe adenovirus infection. The information presented in this review may elucidate the pathogenesis of adenovirus infection, and help to develop new features for prevention and treatment.
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Nikitenko, N. A., T. Speiseder, E. Lam, P. M. Rubtsov, Kh D. Tonaeva, S. A. Borzenok, T. Dobner, and V. S. Prassolov. "Regulation of Human Adenovirus Replication by RNA Interference." Acta Naturae 7, no. 3 (September 15, 2015): 100–107. http://dx.doi.org/10.32607/20758251-2015-7-3-100-107.
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Adenoviruses cause a wide variety of human infectious diseases. Adenoviral conjunctivitis and epidemic keratoconjunctivitis are commonly associated with human species D adenoviruses. Currently, there is no sufficient or appropriate treatment to counteract these adenovirus infections. Thus, there is an urgent need for new etiology-directed therapies with selective activity against human adenoviruses. To address this problem, the adenoviral early genes E1A and E2B (viral DNA polymerase) seem to be promising targets. Here, we propose an effective approach to downregulate the replication of human species D adenoviruses by means of RNA interference. We generated E1A expressing model cell lines enabling fast evaluation of the RNA interference potential. Small interfering RNAs complementary to the E1A mRNA sequences of human species D adenoviruses mediate significant suppression of the E1A expression in model cells. Furthermore, we observed a strong downregulation of replication of human adenoviruses type D8 and D37 by small hairpin RNAs complementary to the E1A or E2B mRNA sequences in primary human limbal cells. We believe that our results will contribute to the development of efficient anti-adenoviral therapy.
4
Zhu, Jiangao, Xiaopei Huang, and Yiping Yang. "Innate Immune Response to Adenoviral Vectors Is Mediated by both Toll-Like Receptor-Dependent and -Independent Pathways." Journal of Virology 81, no. 7 (January 17, 2007): 3170–80. http://dx.doi.org/10.1128/jvi.02192-06.
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ABSTRACT Recombinant adenoviral vectors have been widely used for gene therapy applications and as vaccine vehicles for treating infectious diseases such as human immunodeficiency virus disease. The innate immune response to adenoviruses represents the most significant hurdle in clinical application of adenoviral vectors for gene therapy, but it is an attractive feature for vaccine development. How adenovirus activates innate immunity remains largely unknown. Here we showed that adenovirus elicited innate immune response through the induction of high levels of type I interferons (IFNs) by both plasmacytoid dendritic cells (pDCs) and non-pDCs such as conventional DCs and macrophages. The innate immune recognition of adenovirus by pDCs was mediated by Toll-like receptor 9 (TLR9) and was dependent on MyD88, whereas that by non-pDCs was TLR independent through cytosolic sensing of adenoviral DNA. Furthermore, type I IFNs were pivotal in innate and adaptive immune responses to adenovirus in vivo, and type I IFN blockade diminished immune responses, resulting in more stable transgene expression and reduction of inflammation. These findings indicate that adenovirus activates innate immunity by its DNA through TLR-dependent and -independent pathways in a cell type-specific fashion, and they highlight a critical role for type I IFNs in innate and adaptive immune responses to adenoviral vectors. Our results that suggest strategies to interfere with type I IFN pathway may improve the outcome of adenovirus-mediated gene therapy, whereas approaches to activate the type I IFN pathway may enhance vaccine potency.
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Liu, Minli, Lefang Jiang, Weihua Cao, Jianguo Wu, and Xulin Chen. "Identification of Inhibitors and Drug Targets for Human Adenovirus Infections." Viruses 14, no. 5 (May 4, 2022): 959. http://dx.doi.org/10.3390/v14050959.
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Adenoviruses can cause infections in people of all ages at all seasons of the year. Adenovirus infections cause mild to severe illnesses. Children, immunocompromised patients, or those with existing respiratory or cardiac disease are at higher risk. Unfortunately, there are no commercial drugs or vaccines available on the market for adenovirus infections. Therefore, there is an urgent need to discover new antiviral drugs or drug targets for adenovirus infections. To identify potential antiviral agents for adenovirus infections, we screened a drug library containing 2138 compounds, most of which are drugs with known targets and past phase I clinical trials. On a cell-based assay, we identified 131 hits that inhibit adenoviruses type 3 and 5. A secondary screen confirmed the antiviral effects of 59 inhibitors that inhibit the replication of adenoviruses type 3 or 5. Most of the inhibitors target heat shock protein, protein tyrosine kinase, the mTOR signaling pathway, and other host factors, suggesting that these host factors may be essential for replicating adenoviruses. Through this study, the newly identified adenovirus inhibitors may provide a start point for developing new antiviral drugs to treat adenovirus infections. Further validation of the identified drug targets can help the development of new therapeutics against adenovirus infections.
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Kulanayake, Shermila, and Suresh K. Tikoo. "Adenovirus Core Proteins: Structure and Function." Viruses 13, no. 3 (February 28, 2021): 388. http://dx.doi.org/10.3390/v13030388.
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Adenoviruses have served as a model for investigating viral-cell interactions and discovering different cellular processes, such as RNA splicing and DNA replication. In addition, the development and evaluation of adenoviruses as the viral vectors for vaccination and gene therapy has led to detailed investigations about adenovirus biology, including the structure and function of the adenovirus encoded proteins. While the determination of the structure and function of the viral capsid proteins in adenovirus biology has been the subject of numerous reports, the last few years have seen increased interest in elucidating the structure and function of the adenovirus core proteins. Here, we provide a review of research about the structure and function of the adenovirus core proteins in adenovirus biology.
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Perkins, Laura E. Leigh, Raymond P. Campagnoli, Barry G. Harmon, Christopher R. Gregory, W. L. Steffens, Ken Latimer, Susan Clubb, and Maria Crane. "Detection and Confirmation of Reptilian Adenovirus Infection by in Situ Hybridization." Journal of Veterinary Diagnostic Investigation 13, no. 4 (July 2001): 365–68. http://dx.doi.org/10.1177/104063870101300418.
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Adenovirus infections are documented in at least 12 different species of reptiles. In contrast to their mammalian and avian counterparts reptilian adenoviruses are not well characterized as to their pathogenic potential and their ability to cause primary disease. In the diagnostic setting, fresh tissues are often not available for virus isolation, and the confirmation of reptilian adenovirus infections is dependent largely upon electron microscopy for the identification of intranuclear viral inclusions associated with histopathologic changes. The diagnosis of adenovirus infection in 2 different species of snake was confirmed by the application of DNA in situ hybridization. Using an aviadenovirus specific oligoprobe, adenoviral DNA was observed in the nuclei of hepatocytes, Kupffer cells, endothelial cells, and enterocytes. Electron microscopy of the liver confirmed the presence of intranuclear viral particles morphologically consistent with an adenovirus. DNA in situ hybridization on formalin-fixed tissues can serve as a suitable alternative to electron microscopy in the diagnosis of reptilian adenovirus infections. Both affected snakes had other concurrent diseases, suggesting that the adenovirus may not have been the primary pathogen.
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Rajaiya, Jaya, Amrita Saha, Ashrafali M. Ismail, Xiaohong Zhou, Ting Su, and James Chodosh. "Adenovirus and the Cornea: More Than Meets the Eye." Viruses 13, no. 2 (February 13, 2021): 293. http://dx.doi.org/10.3390/v13020293.
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Human adenoviruses cause disease at multiple mucosal sites, including the respiratory, gastrointestinal, and genitourinary tracts, and are common agents of conjunctivitis. One site of infection that has received sparse attention is the cornea, a transparent tissue and the window of the eye. While most adenovirus infections are self-limited, corneal inflammation (keratitis) due to adenovirus can persist or recur for months to years after infection, leading to reduced vision, discomfort, and light sensitivity. Topical corticosteroids effectively suppress late adenovirus keratitis but are associated with vision-threatening side effects. In this short review, we summarize current knowledge on infection of the cornea by adenoviruses, including corneal epithelial cell receptors and determinants of corneal tropism. We briefly discuss mechanisms of stromal keratitis due to adenovirus infection, and review an emerging therapy to mitigate adenovirus corneal infections based on evolving knowledge of corneal epithelial receptor usage.
9
Guo, Xiaojuan, Yangyang Sun, Juan Chen, Xiaohui Zou, Wenzhe Hou, Wenjie Tan, Tao Hung, and Zhuozhuang Lu. "Restriction-Assembly: A Solution to Construct Novel Adenovirus Vector." Viruses 14, no. 3 (March 6, 2022): 546. http://dx.doi.org/10.3390/v14030546.
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Gene therapy and vaccine development need more novel adenovirus vectors. Here, we attempt to provide strategies to construct adenovirus vectors based on restriction-assembly for researchers with little experience in this field. Restriction-assembly is a combined method of restriction digestion and Gibson assembly, by which the major part of the obtained plasmid comes from digested DNA fragments instead of PCR products. We demonstrated the capability of restriction-assembly in manipulating the genome of simian adenovirus 1 (SAdV-1) in this study. A PCR product of the plasmid backbone was combined with SAdV-1 genomic DNA to construct an infectious clone, plasmid pKSAV1, by Gibson assembly. Restriction-assembly was performed repeatedly in the steps of intermediate plasmid isolation, modification, and restoration. The generated adenoviral plasmid was linearized by restriction enzyme digestion and transfected into packaging 293 cells to rescue E3-deleted replication-competent SAdV1XE3-CGA virus. Interestingly, SAdV1XE3-CGA could propagate in human chronic myelogenous leukemia K562 cells. The E1 region was similarly modified to generate E1/E3-deleted replication-defective virus SAdV1-EG. SAdV1-EG had a moderate gene transfer ability to adherent mammalian cells, and it could efficiently transduce suspension cells when compared with the human adenovirus 5 control vector. Restriction-assembly is easy to use and can be performed without special experimental materials and instruments. It is highly effective with verifiable outcomes at each step. More importantly, restriction-assembly makes the established vector system modifiable, upgradable and under sustainable development, and it can serve as the instructive method or strategy for the synthetic biology of adenoviruses.
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Blanchette, Paola, and Jose G. Teodoro. "A Renaissance for Oncolytic Adenoviruses?" Viruses 15, no. 2 (January 26, 2023): 358. http://dx.doi.org/10.3390/v15020358.
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In the 1990s, adenovirus became one of the first virus types to be genetically engineered to selectively destroy cancer cells. In the intervening years, the field of “oncolytic viruses” has slowly progressed and culminated in 2015 with the FDA approval of Talimogene laherparepvec, a genetically engineered herpesvirus, for the treatment of metastatic melanoma. Despite the slower progress in translating oncolytic adenovirus to the clinic, interest in the virus remains strong. Among all the clinical trials currently using viral oncolytic agents, the largest proportion of these are using recombinant adenovirus. Many trials are currently underway to use oncolytic virus in combination with immune checkpoint inhibitors (ICIs), and early results using oncolytic adenovirus in this manner are starting to show promise. Many of the existing strategies to engineer adenoviruses were designed to enhance selective tumor cell replication without much regard to interactions with the immune system. Adenovirus possesses a wide range of viral factors to attenuate both innate anti-viral pathways and immune cell killing. In this review, we summarize the strategies of oncolytic adenoviruses currently in clinical trials, and speculate how the mutational backgrounds of these viruses may impact upon the efficacy of these agents in oncolytic and immunotherapy. Despite decades of research on human adenoviruses, the interactions that these viruses have with the immune system remains one of the most understudied aspects of the virus and needs to be improved to rationally design the next generation of engineered viruses.
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Jiang, Sunny C., Jijun Han, Jian-Wen He, and Weiping Chu. "Evaluation of four cell lines for assay of infectious adenoviruses in water samples." Journal of Water and Health 7, no. 4 (July 1, 2009): 650–56. http://dx.doi.org/10.2166/wh.2009.088.
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Human viral contamination in drinking and recreational waters poses health risks. The application of PCR-based molecular technology has advanced our knowledge of the occurrence and prevalence of human viruses in water; however, it has provided no information on viral viability and infectivity. Four human cell lines were compared for their sensitivity to different serotypes of human adenoviruses using the TCID50 test. The sensitivity of each cell line varied with different serotypes of adenovirus. Human embryonic kidney cell line 293A and human lung carcinoma cell line A549 were the most sensitive, especially to enteric adenovirus 40 and 41. Plaque assay of primary sewage samples showed 293A can detect viral plaques in 7 of 13 primary sewage samples tested. Adenoviruses were also isolated using 293A from environmental water concentrates. Cloning and sequencing of environmental adenoviral isolates indentified them to be aligned with adenoviruses serotype 40 and serotype 5. The result of this study suggests that plaque assay with 293A cell line is suitable for detection of adenovirus in the aquatic environment. Combining this cell culture with molecular methods for viral assay in the aquatic environment will provide critical information for risk assessment.
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TEUNIS, P., J. SCHIJVEN, and S. RUTJES. "A generalized dose-response relationship for adenovirus infection and illness by exposure pathway." Epidemiology and Infection 144, no. 16 (August 30, 2016): 3461–73. http://dx.doi.org/10.1017/s0950268816001862.
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SUMMARYAdenoviruses are found everywhere in the environment, and cause various health problems including symptoms of enteric illness, and respiratory illness. Despite their significance to public health, few studies have addressed the health risks associated with exposure to adenovirus. Human challenge studies have been published for a few adenoviruses, which involved exposure through oral ingestion, inhalation, intranasal and intraocular droplet inoculation. Nothwithstanding the different symptoms resulting from such exposures, infection can be defined as colonization of a corresponding mucosa. A two-level dose-response model was developed to describe the distributions of infectivity and pathogenicity in various challenge studies of adenovirus, incorporating differences in inoculation route as shift in average infectivity and pathogenicity. This dose-response model can be used to make predictions for the infectivity of adenovirus, specific to any of the four studied inoculation methods. The generalized adenovirus dose-response relationship for infection and acute illness takes into account variation in infectivity and/or pathogenicity across adenovirus types, as well as uncertainty due to limited data.
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Rajaiya, Jaya, Amrita Saha, Xiaohong Zhou, and James Chodosh. "Human Adenovirus Species D Interactions with Corneal Stromal Cells." Viruses 13, no. 12 (December 14, 2021): 2505. http://dx.doi.org/10.3390/v13122505.
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Notable among the many communicable agents known to infect the human cornea is the human adenovirus, with less than ten adenoviruses having corneal tropism out of more than 100 known types. The syndrome of epidemic keratoconjunctivitis (EKC), caused principally by human adenovirus, presents acutely with epithelial keratitis, and later with stromal keratitis that can be chronic and recurrent. In this review, we discuss the current state of knowledge regarding the molecular biology of adenovirus infection of corneal stromal cells, among which the fibroblast-like keratocyte is the most predominant, in order to elucidate basic pathophysiologic mechanisms of stromal keratitis in the human patient with EKC.
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Sallard, Erwan, Wenli Zhang, Malik Aydin, Katrin Schröer, and Anja Ehrhardt. "The Adenovirus Vector Platform: Novel Insights into Rational Vector Design and Lessons Learned from the COVID-19 Vaccine." Viruses 15, no. 1 (January 11, 2023): 204. http://dx.doi.org/10.3390/v15010204.
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The adenovirus vector platform remains one of the most efficient toolboxes for generation of transfer vehicles used in gene therapy and virotherapy to treat tumors, as well as vaccines to protect from infectious diseases. The adenovirus genome and capsids can be modified using highly efficient techniques, and vectors can be produced at high titers, which facilitates their rapid adaptation to current needs and disease applications. Over recent years, the adenovirus vector platform has been in the center of attention for vaccine development against the ongoing coronavirus SARS-CoV-2/COVID-19 pandemic. The worldwide deployment of these vaccines has greatly deepened the knowledge on virus-host interactions and highlighted the need to further improve the effectiveness and safety not only of adenovirus-based vaccines but also of gene therapy and oncolytic virotherapy vectors. Based on the current evidence, we discuss here how adenoviral vectors can be further improved by intelligent molecular design. This review covers the full spectrum of state-of-the-art strategies to avoid vector-induced side effects ranging from the vectorization of non-canonical adenovirus types to novel genome engineering techniques.
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Karen, Kasey A., Cailin Deal, Robert J. Adams, Carolyn Nielsen, Cameron Ward, Diego A. Espinosa, Jane Xie, Fidel Zavala, and Gary Ketner. "A Replicating Adenovirus Capsid Display Recombinant Elicits Antibodies against Plasmodium falciparum Sporozoites in Aotus nancymaae Monkeys." Infection and Immunity 83, no. 1 (November 3, 2014): 268–75. http://dx.doi.org/10.1128/iai.02626-14.
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Decades of success with live adenovirus vaccines suggest that replication-competent recombinant adenoviruses (rAds) could serve as effective vectors for immunization against other pathogens. To explore the potential of a live rAd vaccine against malaria, we prepared a viable adenovirus 5 (Ad5) recombinant that displays a B-cell epitope from the circumsporozoite protein (CSP) ofPlasmodium falciparumon the virion surface. The recombinant inducedP. falciparumsporozoite-neutralizing antibodies in mice. Human adenoviruses do not replicate in mice. Therefore, to examine immunogenicity in a system in which, as in humans, the recombinant replicates, we constructed a similar recombinant in an adenovirus mutant that replicates in monkey cells and immunized fourAotus nancymaaemonkeys. The recombinant replicated in the monkeys after intratracheal instillation, the first demonstration of replication of human adenoviruses in New World monkeys. Immunization elicited antibodies both to thePlasmodiumepitope and the Ad5 vector. Antibodies from all four monkeys recognized CSP on intact parasites, and plasma from one monkey neutralized sporozoitesin vitroand conferred partial protection againstP. falciparumsporozoite infection after passive transfer to mice. Prior enteric inoculation of two animals with antigenically wild-type adenovirus primed a response to the subsequent intratracheal inoculation, suggesting a route to optimizing performance. A vaccine is not yet available againstP. falciparum, which induces the deadliest form of malaria and kills approximately one million children each year. The live capsid display recombinant described here may constitute an early step in a critically needed novel approach to malaria immunization.
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Mo, Jongseo. "Historical Investigation of Fowl Adenovirus Outbreaks in South Korea from 2007 to 2021: A Comprehensive Review." Viruses 13, no. 11 (November 10, 2021): 2256. http://dx.doi.org/10.3390/v13112256.
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Fowl adenoviruses (FAdVs) have long been recognized as critical viral pathogens within the poultry industry, associated with severe economic implications worldwide. This specific group of viruses is responsible for a broad spectrum of diseases in birds, and an increasing occurrence of outbreaks was observed in the last ten years. Since their first discovery forty years ago in South Korea, twelve antigenically distinct serotypes of fowl adenoviruses have been described. This comprehensive review covers the history of fowl adenovirus outbreaks in South Korea and updates the current epidemiological landscape of serotype diversity and replacement as well as challenges in developing effective broadly protective vaccines. In addition, transitions in the prevalence of dominant fowl adenovirus serotypes from 2007 to 2021, alongside the history of intervention strategies, are brought into focus. Finally, future aspects are also discussed.
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Sato-Dahlman, Mizuho, and Masato Yamamoto. "The Development of Oncolytic Adenovirus Therapy in the Past and Future - For the Case of Pancreatic Cancer." Current Cancer Drug Targets 18, no. 2 (January 15, 2018): 153–61. http://dx.doi.org/10.2174/1568009617666170222123925.
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Pancreatic cancer is an aggressive malignant disease and the efficacy of current treatments for unresectable diseases is quite limited despite recent advances. Gene therapy /virotherapy strategies may provide new options for the treatment of various cancers including pancreatic cancer. Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal effect in a variety of cancers and it has been employed for the development of potent oncolytic virotherapy agents for pancreatic cancer. Our ultimate goal is to develop an oncolytic adenovirus enabling the treatment of patients with advanced or spread diseases by systemic injection. Systemic application of oncolytic therapy mandates more efficient and selective gene delivery and needs to embody sufficient antitumor effect even with limited initial delivery to the tumor location. In this review, the current status of oncolytic adenoviruses from the viewpoints of vector design and potential strategies to overcome current obstacles for its clinical application will be described. We will also discuss the efforts to improve the antitumor activity of oncolytic adenovirus, in in vivo animal models, and the combination therapy of oncolytic adenovirus with radiation and chemotherapy.
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Tabrizi, Sepehr N., Alison E. Ling, Catriona S. Bradshaw, Christopher K. Fairley, and Suzanne M. Garland. "Human adenoviruses types associated with non-gonococcal urethritis." Sexual Health 4, no. 1 (2007): 41. http://dx.doi.org/10.1071/sh06054.
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Background: Role of adenoviruses in non-gonococcal urethritis (NGU) has been reported in only a few studies. The aim of the study was to detect and type adenoviruses in men presenting with NGU. Methods: 636 heterosexual and homosexual men presenting with NGU from Melbourne, Australia were recently evaluated for various aetiological organisms including adenovirus. We utilised methods including polymerase chain reaction for detection followed by sequence analysis to type positive samples. Results: Overall, 12 samples from patients with NGU had adenovirus detected. Five types were identified: type 4 (subgenus E), type 35 (subgenus B), and types 9, 37 and 49 (subgenus D). The presence of mixed adenovirus strains was not detected in any sample. Conclusion: Overall, subgenus B, D and E were predominant in this patient population.
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Athukorala, Ajani, Jade K. Forwood, David N. Phalen, and Subir Sarker. "Molecular Characterisation of a Novel and Highly Divergent Passerine Adenovirus 1." Viruses 12, no. 9 (September 17, 2020): 1036. http://dx.doi.org/10.3390/v12091036.
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Wild birds harbour a large number of adenoviruses that remain uncharacterised with respect to their genomic organisation, diversity, and evolution within complex ecosystems. Here, we present the first complete genome sequence of an atadenovirus from a passerine bird that is tentatively named Passerine adenovirus 1 (PaAdV-1). The PaAdV-1 genome is 39,664 bp in length, which was the longest atadenovirus to be sequenced, to the best of our knowledge, and contained 42 putative genes. Its genome organisation was characteristic of the members of genus Atadenovirus; however, the novel PaAdV-1 genome was highly divergent and showed the highest sequence similarity with psittacine adenovirus-3 (55.58%). Importantly, PaAdV-1 complete genome was deemed to contain 17 predicted novel genes that were not present in any other adenoviruses sequenced to date, with several of these predicted novel genes encoding proteins that harbour transmembrane helices. Subsequent analysis of the novel PaAdV-1 genome positioned phylogenetically to a distinct sub-clade with all others sequenced atadenoviruses and did not show any obvious close evolutionary relationship. This study concluded that the PaAdV-1 complete genome described here is not closely related to any other adenovirus isolated from avian or other natural host species and that it should be considered a separate species.
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Esford, L. E., and Y. Haj-Ahmad. "Sequence Analysis of the Putative E3 Region of Bovine Adenovirus Type 2." Intervirology 37, no. 5 (1994): 277–86. http://dx.doi.org/10.1159/000150389.
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Adenoviruses are nonenveloped icosahedral-shaped particles. The double-stranded viral DNA genome contains four major early transcription units, designated El (a and b), E2 (a and b), E3 and E4, which are expressed in a regulated manner soon after infection. The gene products of the region E3, shown to be nonessential for viral replication in vitro, are believed to be involved in counteracting host immunosurveillance. Human adenovirus type 5 DNA sequences of transcription units L4 and L5 adjacent to E3 were used to localize E3 within the bovine adenovirus type 2. The DNA sequences between 74.8 and 84.4 mu containing E3 and the fiber gene were determined. The E3 region was found to consist of about 2.3 kb pairs and to encode four proteins longer than 60 amino acids. However, these four open reading frames did not show significant homology to any other known adenovirus DNA or protein sequence.
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Singh, Gurdeep, Ashrafali M. Ismail, Jeong Yoon Lee, Mirja Ramke, Ji Sun Lee, David W. Dyer, Donald Seto, Jaya Rajaiya, and and James Chodosh. "Divergent Evolution of E1A CR3 in Human Adenovirus Species D." Viruses 11, no. 2 (February 8, 2019): 143. http://dx.doi.org/10.3390/v11020143.
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Adenovirus E1A is the first viral protein expressed during infection. E1A controls critical aspects of downstream viral gene expression and cell cycle deregulation, and its function is thought to be highly conserved among adenoviruses. Various bioinformatics analyses of E1A from 38 human adenoviruses of species D (HAdV-D), including likelihood clade model partitioning, provided highly significant evidence of divergence of HAdV-Ds into two distinct groups for the conserved region 3 (CR3), present only in the E1A 13S isoform. This variance within E1A 13S of HAdV-Ds was not found in any other human adenovirus (HAdV) species. By protein sequence and structural analysis, the zinc finger motif of E1A CR3, previously shown as critical for transcriptional activation, showed the greatest differences. Subsequent codon usage bias analysis revealed substantial divergence in E1A 13S between the two groups of HAdV-Ds, suggesting that these two sub-groups of HAdV-D evolved under different cellular conditions. Hence, HAdV-D E1A embodies a previously unappreciated evolutionary divergence among HAdVs.
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Pollack, Alisa, and Rick Varma. "Adenovirus-associated paraphimosis." International Journal of STD & AIDS 30, no. 8 (May 9, 2019): 825–27. http://dx.doi.org/10.1177/0956462419842448.
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We present the first reported case of paraphimosis associated with concurrent adenoviral urethritis and conjunctivitis in a heterosexual man. This case reinforces the need to consider adenovirus in the differential diagnosis of non-gonococcal urethritis and describes a potentially serious complication.
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Ajuebor, Maureen, and Qingling Chen. "Intrahepatic Vα14iNKT cells Promote Liver Pathology during Adenovirus infection by Regulating Hepatic CCL5 and Intrahepatic γδT cell Activation: Implications for Vaccine Development (89.2)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 89.2. http://dx.doi.org/10.4049/jimmunol.184.supp.89.2.
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Abstract Replication-defective recombinant Adenoviruses are potential innovative viral vaccine vectors for treating many inherited and acquired human diseases. Broad clinical application of Adenoviruses in vaccine development is being hindered by the induction of vigorous innate and adaptive immune responses against the vector resulting in loss of Adenovirus transgene and deleterious effects in the liver. Vα14iNKT cells are thymic-derived innate T cells at the interface between the two arms of the immune response. The pathophysiological role of Vα14iNKT cells during replication-defective Adenovirus infection is not known, and is therefore a focus of our study. Our results revealed that Vα14iNKT cells were activated in response to Adenovirus infection to produce hepatic CCL5. In vivo studies utilizing CCL5 deficient mice showed that CCL5 deficiency caused reduced liver pathology and Adenovirus transgene loss. Similar results were also seen after blocking the biological effects of CCL5 receptors. Additionally, our data also revealed a novel and previously unrecognized pro-inflammatory role for activated intrahepatic Vα14iNKT cells in promoting liver pathology by positively regulating intrahepatic γδT cell activation. In summary, we have identified a novel and important pro-inflammatory role for activated intrahepatic Vα14iNKT cells in positively regulating both hepatic CCL5 and activated intrahepatic γδT cells to induce liver pathology without loss of Adenovirus transgene.
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Afrough, Sara, Sophie Rhodes, Thomas Evans, Richard White, and John Benest. "Immunologic Dose-Response to Adenovirus-Vectored Vaccines in Animals and Humans: A Systematic Review of Dose-Response Studies of Replication Incompetent Adenoviral Vaccine Vectors when Given via an Intramuscular or Subcutaneous Route." Vaccines 8, no. 1 (March 17, 2020): 131. http://dx.doi.org/10.3390/vaccines8010131.
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Optimal vaccine dosing is important to ensure the greatest protection and safety. Analysis of dose-response data, from previous studies, may inform future studies to determine the optimal dose. Implementing more quantitative modelling approaches in vaccine dose finding have been recently suggested to accelerate vaccine development. Adenoviral vectored vaccines are in advanced stage of development for a variety of prophylactic and therapeutic indications, however dose-response has not yet been systematically determined. To further inform adenoviral vectored vaccines dose identification, historical dose-response data should be systematically reviewed. A systematic literature review was conducted to collate and describe the available dose-response studies for adenovirus vectored vaccines. Of 2787 papers identified by Medline search strategy, 35 were found to conform to pre-defined criteria. The majority of studies were in mice or humans and studied adenovirus serotype 5. Dose-response data were available for 12 different immunological responses. The majority of papers evaluated three dose levels, only two evaluated more than five dose levels. The most common dosing range was 107–1010 viral particles in mouse studies and 108–1011 viral particles in human studies. Data were available on adenovirus vaccine dose-response, primarily on adenovirus serotype 5 backbones and in mice and humans. These data could be used for quantitative adenoviral vectored vaccine dose optimisation analysis.
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Atasheva, Svetlana, and Dmitry M. Shayakhmetov. "Cytokine Responses to Adenovirus and Adenovirus Vectors." Viruses 14, no. 5 (April 24, 2022): 888. http://dx.doi.org/10.3390/v14050888.
Full textAbstract:
The expression of cytokines and chemokines in response to adenovirus infection is tightly regulated by the innate immune system. Cytokine-mediated toxicity and cytokine storm are known clinical phenomena observed following naturally disseminated adenovirus infection in immunocompromised hosts as well as when extremely high doses of adenovirus vectors are injected intravenously. This dose-dependent, cytokine-mediated toxicity compromises the safety of adenovirus-based vectors and represents a critical problem, limiting their utility for gene therapy applications and the therapy of disseminated cancer, where intravenous injection of adenovirus vectors may provide therapeutic benefits. The mechanisms triggering severe cytokine response are not sufficiently understood, prompting efforts to further investigate this phenomenon, especially in clinically relevant settings. In this review, we summarize the current knowledge on cytokine and chemokine activation in response to adenovirus- and adenovirus-based vectors and discuss the underlying mechanisms that may trigger acute cytokine storm syndrome. First, we review profiles of cytokines and chemokines that are activated in response to adenovirus infection initiated via different routes. Second, we discuss the molecular mechanisms that lead to cytokine and chemokine transcriptional activation. We further highlight how immune cell types in different organs contribute to synthesis and systemic release of cytokines and chemokines in response to adenovirus sensing. Finally, we review host factors that can limit cytokine and chemokine expression and discuss currently available and potential future interventional approaches that allow for the mitigation of the severity of the cytokine storm syndrome. Effective cytokine-targeted interventional approaches may improve the safety of systemic adenovirus delivery and thus broaden the potential clinical utility of adenovirus-based therapeutic vectors.
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Atasheva, Svetlana, and Dmitry M. Shayakhmetov. "Cytokine Responses to Adenovirus and Adenovirus Vectors." Viruses 14, no. 5 (April 24, 2022): 888. http://dx.doi.org/10.3390/v14050888.
Full textAbstract:
The expression of cytokines and chemokines in response to adenovirus infection is tightly regulated by the innate immune system. Cytokine-mediated toxicity and cytokine storm are known clinical phenomena observed following naturally disseminated adenovirus infection in immunocompromised hosts as well as when extremely high doses of adenovirus vectors are injected intravenously. This dose-dependent, cytokine-mediated toxicity compromises the safety of adenovirus-based vectors and represents a critical problem, limiting their utility for gene therapy applications and the therapy of disseminated cancer, where intravenous injection of adenovirus vectors may provide therapeutic benefits. The mechanisms triggering severe cytokine response are not sufficiently understood, prompting efforts to further investigate this phenomenon, especially in clinically relevant settings. In this review, we summarize the current knowledge on cytokine and chemokine activation in response to adenovirus- and adenovirus-based vectors and discuss the underlying mechanisms that may trigger acute cytokine storm syndrome. First, we review profiles of cytokines and chemokines that are activated in response to adenovirus infection initiated via different routes. Second, we discuss the molecular mechanisms that lead to cytokine and chemokine transcriptional activation. We further highlight how immune cell types in different organs contribute to synthesis and systemic release of cytokines and chemokines in response to adenovirus sensing. Finally, we review host factors that can limit cytokine and chemokine expression and discuss currently available and potential future interventional approaches that allow for the mitigation of the severity of the cytokine storm syndrome. Effective cytokine-targeted interventional approaches may improve the safety of systemic adenovirus delivery and thus broaden the potential clinical utility of adenovirus-based therapeutic vectors.
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Atasheva, Svetlana, and Dmitry M. Shayakhmetov. "Cytokine Responses to Adenovirus and Adenovirus Vectors." Viruses 14, no. 5 (April 24, 2022): 888. http://dx.doi.org/10.3390/v14050888.
Full textAbstract:
The expression of cytokines and chemokines in response to adenovirus infection is tightly regulated by the innate immune system. Cytokine-mediated toxicity and cytokine storm are known clinical phenomena observed following naturally disseminated adenovirus infection in immunocompromised hosts as well as when extremely high doses of adenovirus vectors are injected intravenously. This dose-dependent, cytokine-mediated toxicity compromises the safety of adenovirus-based vectors and represents a critical problem, limiting their utility for gene therapy applications and the therapy of disseminated cancer, where intravenous injection of adenovirus vectors may provide therapeutic benefits. The mechanisms triggering severe cytokine response are not sufficiently understood, prompting efforts to further investigate this phenomenon, especially in clinically relevant settings. In this review, we summarize the current knowledge on cytokine and chemokine activation in response to adenovirus- and adenovirus-based vectors and discuss the underlying mechanisms that may trigger acute cytokine storm syndrome. First, we review profiles of cytokines and chemokines that are activated in response to adenovirus infection initiated via different routes. Second, we discuss the molecular mechanisms that lead to cytokine and chemokine transcriptional activation. We further highlight how immune cell types in different organs contribute to synthesis and systemic release of cytokines and chemokines in response to adenovirus sensing. Finally, we review host factors that can limit cytokine and chemokine expression and discuss currently available and potential future interventional approaches that allow for the mitigation of the severity of the cytokine storm syndrome. Effective cytokine-targeted interventional approaches may improve the safety of systemic adenovirus delivery and thus broaden the potential clinical utility of adenovirus-based therapeutic vectors.
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Gainor, Kerry, Anne A. M. J. Becker, Yashpal S. Malik, and Souvik Ghosh. "First Report on Detection and Molecular Characterization of Adenoviruses in the Small Indian Mongoose (Urva auropunctata)." Viruses 13, no. 11 (October 30, 2021): 2194. http://dx.doi.org/10.3390/v13112194.
Full textAbstract:
Using a broad-range nested PCR assay targeting the DNA-dependent DNA polymerase (pol) gene, we detected adenoviruses in 17 (20.48%) out of 83 fecal samples from small Indian mongooses (Urva auropunctata) on the Caribbean island of St. Kitts. All 17 PCR amplicons were sequenced for the partial pol gene (~300 bp, hereafter referred to as Mon sequences). Fourteen of the 17 Mon sequences shared maximum homology (98.3–99.6% and 97–98.9% nucleotide (nt) and deduced amino acid (aa) sequence identities, respectively) with that of bovine adenovirus-6 (species Bovine atadenovirus E). Mongoose-associated adenovirus Mon-39 was most closely related (absolute nt and deduced aa identities) to an atadenovirus from a tropical screech owl. Mon-66 shared maximum nt and deduced aa identities of 69% and 71.4% with those of atadenoviruses from a spur-thighed tortoise and a brown anole lizard, respectively. Phylogenetically, Mon-39 and Mon-66 clustered within clades that were predominated by atadenoviruses from reptiles, indicating a reptilian origin of these viruses. Only a single mongoose-associated adenovirus, Mon-34, was related to the genus Mastadenovirus. However, phylogenetically, Mon-34 formed an isolated branch, distinct from other mastadenoviruses. Since the fecal samples were collected from apparently healthy mongooses, we could not determine whether the mongoose-associated adenoviruses infected the host. On the other hand, the phylogenetic clustering patterns of the mongoose-associated atadenoviruses pointed more towards a dietary origin of these viruses. Although the present study was based on partial pol sequences (~90 aa), sequence identities and phylogenetic analysis suggested that Mon-34, Mon-39, and Mon-66 might represent novel adenoviruses. To our knowledge, this is the first report on the detection and molecular characterization of adenoviruses from the mongoose.
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Allayeh, Abdou Kamal, Sahar Abd Al-Daim, Nehal Ahmed, Mona El-Gayar, and Ahmed Mostafa. "Isolation and Genotyping of Adenoviruses from Wastewater and Diarrheal Samples in Egypt from 2016 to 2020." Viruses 14, no. 10 (October 4, 2022): 2192. http://dx.doi.org/10.3390/v14102192.
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Human adenoviruses (HAdV) are a prevalent cause of diarrhea in children all over the world. Adenoviral infections are responsible for 2% to 10% of diarrheic cases. A long-term investigation was required to gain better knowledge about the incidence of HAdV in Egypt. Herein, we conducted 5 years of detection, isolation, and genotyping of HAdV in fecal and sewage samples from 2016 to 2020, in Cairo, Egypt using molecular and cell culture assays. Human adenoviruses were identified in 35 of 447 fecal samples (7.8%), but only 53.3% (64/120) of the sewage samples. Children under the age of two had the highest positive rate for HAdV infection (77.1%). Species F of HAdV was the most common prevalent genotype in fecal and sewage samples, at 88.5% and 85.9%, respectively. The most prevalent genotypes detected in fecal samples were HAdV-41 (71.2%), HAdV-40 (17.2%), HAdV-6 (5.7%), and HAdV-1 (5.7%). In contrast, the most common genotypes in sewage samples were HAdV-41 (64%), HAdVs-40 (21.8%), HAdV-6 (7.8%), HAdV-1 (4.7%), and HAdV-2 (1.6%). HAdV was detected in all months of the year, with a peak period for clinical samples from December to February (p < 0.001), which matched Egypt’s rainy season, while the monthly distribution of HAdV in sewage samples remained consistent throughout the year, with no statistically significant peak period. Interestingly, the HAdV-type 41 genotype was the most common genotype during all of the years of this study. Throughout a 5-year period, our work revealed the infection rate, seasonal distribution, virus isolates, and genetic diversity of HAdV infections in environmental and clinical samples in Cairo, Egypt. Non-enteric adenovirus types (1, 2 and 6), as well as enteric adenovirus (41 and 40), may play a key role in gastroenteritis in Egypt.
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Karimi, Ali, Mohammad-Taghi Moradi, Mohammad Rabiei, and Somayeh Alidadi. "In vitro anti-adenoviral activities of ethanol extract, fractions, and main phenolic compounds of pomegranate (Punica granatum L.) peel." Antiviral Chemistry and Chemotherapy 28 (January 2020): 204020662091657. http://dx.doi.org/10.1177/2040206620916571.
Full textAbstract:
Background Adenovirus causes a number of diseases in human, and can cause serious infection in severely immunosuppressed individuals. Despite the seriousness of adenovirus infection, there is no definitely approved anti-adenoviral therapy. Many studies have shown that compounds derived from medicinal plants have antiviral activity. Therefore, this study evaluated in vitro anti-adenoviral activity of ethanol extract, fractions, and main phenolic compounds of pomegranate peel. Methods The ethanol extract of pomegranate peel was prepared with maceration method and fractionated by consecutive liquid/liquid partition. The cytotoxic and anti-adenovirus activities of the extract, fractions, and main phenolic compounds (ellagic acid, punicalagin and gallic acid) were evaluated on Hep-2 cell line using MTT assay. Inhibitory effect on adsorption and post-adsorption phases of the virus replication cycle was also evaluated. Results Pomegranate peel extract had a desirable effect against adenovirus with IC50 of 5.77 µg/mL and selectivity index of 49.9. Among the fractions and compounds, the n-butanol fraction and gallic acid had the highest anti-adenoviral activity with IC50 of 2.16 µg/mL and 4.67 µM and selectivity indices of 122.5 and 10.5, respectively. The crude extract, n-butanol fraction and gallic acid inhibited the virus replication in post-adsorption phase ( p < 0.01). Conclusion Pomegranate peel extract, especially its n-butanol fraction, could serve as a new promising anti-adenovirus agent due to high inhibitory effect against adenovirus replication. The effect of the n-butanol fraction may be related to the synergistic effect or other compounds of this fraction. Further understanding of the bioassay guided isolation of natural compounds of this fraction seems essential.
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Daussy, Coralie F., Noémie Pied, and Harald Wodrich. "Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties." Viruses 13, no. 7 (June 24, 2021): 1221. http://dx.doi.org/10.3390/v13071221.
Full textAbstract:
Adenovirus vector-based genetic vaccines have emerged as a powerful strategy against the SARS-CoV-2 health crisis. This success is not unexpected because adenoviruses combine many desirable features of a genetic vaccine. They are highly immunogenic and have a low and well characterized pathogenic profile paired with technological approachability. Ongoing efforts to improve adenovirus-vaccine vectors include the use of rare serotypes and non-human adenoviruses. In this review, we focus on the viral capsid and how the choice of genotypes influences the uptake and subsequent subcellular sorting. We describe how understanding capsid properties, such as stability during the entry process, can change the fate of the entering particles and how this translates into differences in immunity outcomes. We discuss in detail how mutating the membrane lytic capsid protein VI affects species C viruses’ post-entry sorting and briefly discuss if such approaches could have a wider implication in vaccine and/or vector development.
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Folegatti, Pedro M., Duncan Bellamy, Rachel Roberts, Jonathan Powlson, Nick J. Edwards, Catherine F. Mair, Georgina Bowyer, et al. "Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine." Vaccines 7, no. 2 (May 15, 2019): 40. http://dx.doi.org/10.3390/vaccines7020040.
Full textAbstract:
Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens. Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising antibodies. We have constructed a replication deficient simian adenovirus-vectored vaccine (ChAdOx2) expressing 4 genes from the Mycobacterium avium subspecies paratuberculosis (AhpC, Gsd, p12 and mpa). Safety and T-cell immunogenicity results of the first clinical use of the ChAdOx2 vector are presented here. The trial was conducted using a ‘three-plus-three’ dose escalation study design. We demonstrate the vaccine is safe, well tolerated and immunogenic.
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Crabtree, K. D., C. P. Gerba, J. B. Rose, and C. N. Haas. "Waterborne adenovirus: a risk assessment." Water Science and Technology 35, no. 11-12 (June 1, 1997): 1–6. http://dx.doi.org/10.2166/wst.1997.0700.
Full textAbstract:
Adenoviruses have been detected in raw sewage throughout the world and are associated with a number of human illnesses but their occurrence and pathogenicity have not been well studied. A risk assessment approach was used to determine their significance as a waterborne pathogen. There are 47 types of adenoviruses and the diseases resulting from infections include conjunctivitis, pharyngitis, pneumonia, acute and chronic appendicitis, exanthematous disease, bronchiolitis, acute respiratory disease, and gastroenteritis (types 40 and 41). Adenovirus is considered to be only second to rotavirus in terms of its significance as a pathogen of childhood gastroenteritis. Adenovirus infections are usually acute and self-limiting with a greater severity of illness occurring in the immunocompromised (e.g. AIDS patients and transplant recipients). They are reported to be more resistant to inactivation by UV than enteroviruses and are sometimes detected at higher levels in polluted waters. There are documented outbreaks of conjunctivitis due to adenovirus types 3 & 4 associated with swimming in contaminated recreational waters. Based on the data obtained from human dose-response studies, the exponential model [Pi = 1 -exp(-rN); r = 0.4172] was chosen for this risk assessment. Annual risks of infection in drinking water for adenovirus at average levels of 1/1,000L to 1/100L ranged from 8.3/10,000 to 8.3/1,000, respectively. Using monitoring data from a recreational water, risks were calculated to be as high as 1/1,000 for a single exposure.
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Lukashev, Alexander N., Olga E. Ivanova, Tatiana P. Eremeeva, and Richard D. Iggo. "Evidence of frequent recombination among human adenoviruses." Journal of General Virology 89, no. 2 (February 1, 2008): 380–88. http://dx.doi.org/10.1099/vir.0.83057-0.
Full textAbstract:
Genome stability is a prerequisite for the production and use of adenoviruses for therapy of genetic diseases and cancer. To test the premise that the adenoviral genome is stable, the phylogenetic relationships of 16 adenovirus C (AdC) field isolates were studied in four genome regions: hexon, fiber, polymerase and E1A. The phylogenetic relationships in the fiber gene concurred with those in the hexon region. In contrast, the non-structural regions had marks of frequent recombination, to the point that an isolate of one serotype could contain non-structural proteins that were identical to the genes from a different serotype. Our results suggest that recombination among circulating adenoviruses is very frequent and plays an important role in shaping the phylogenetic relationships of adenovirus genomes. Analysis of the available complete genome sequences of AdB, AdC and AdD species showed that recombination shuffles genome fragments within a species, but not between species. One of the AdC field isolates possessed the fiber gene of AdC type 6, but a hexon gene that was distinct from all AdC serotypes. This strain could not be typed unambiguously in a neutralization test and might represent a novel serotype of AdC. Comparison of the right end (nt 18838–33452) of this isolate with that of the ATCC Ad6 strain showed clear evidence of multiple recombination events.
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Ying, Baoling, Ann E. Tollefson, Jacqueline F. Spencer, Lata Balakrishnan, Stephen Dewhurst, Cristina Capella, R. Mark L. Buller, Karoly Toth, and William S. M. Wold. "Ganciclovir Inhibits Human Adenovirus Replication and Pathogenicity in Permissive Immunosuppressed Syrian Hamsters." Antimicrobial Agents and Chemotherapy 58, no. 12 (September 15, 2014): 7171–81. http://dx.doi.org/10.1128/aac.03860-14.
Full textAbstract:
ABSTRACTAdenovirus infections of immunocompromised patients can develop into deadly multiorgan or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for the treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence of the efficacy of these drugs exists. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was previously reported to be effective against human adenovirusesin vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and the animals develop symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its antiadenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5, was used as a positive control in the prophylactic experiment.
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Iglesias-Caballero, Maria, Javier Juste, Sonia Vázquez-Morón, Ana Falcon, Carolina Aznar-Lopez, Carlos Ibáñez, Francisco Pozo, et al. "New Adenovirus Groups in Western Palaearctic Bats." Viruses 10, no. 8 (August 20, 2018): 443. http://dx.doi.org/10.3390/v10080443.
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In the context of long-term screening for viruses on Western Palaearctic bats, we tested for the presence of adenovirus 1392 oropharyngeal swabs and 325 stool samples taken from 27 bat species. Adenoviruses were detected in 12 species of the Vespertilionidae and the Rhinolophidae families. Fifty positive respiratory and 26 positive stool samples were studied. Phylogenetic analyses of partial hexon protein and partial DNA-dependent DNA polymerase genes indicate that all these bat adenoviruses belong to the genus Mastadenovirus but without constituting a monophyletic cluster. According to genetic identities, the new groups are distinct to the previously described Bat mastadenovirus A and B species and contribute with potentially new members. Our data support that diversity of bat mastadenovirus is host-dependent and increase the knowledge of potentially pathogenic virus from bats. Due to the active role of bats as viral reservoirs, the characterization of these viruses is relevant for Public Health.
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Lee, Dongwoo, Jida Liu, Hyun Jung Junn, Eun-Joo Lee, Kyu-Shik Jeong, and Dai-Wu Seol. "No more helper adenovirus: production of gutless adenovirus (GLAd) free of adenovirus and replication-competent adenovirus (RCA) contaminants." Experimental & Molecular Medicine 51, no. 10 (October 2019): 1–18. http://dx.doi.org/10.1038/s12276-019-0334-z.
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Abstract Gene therapy is emerging as an effective treatment option for various inherited genetic diseases. Gutless adenovirus (GLAd), also known as helper-dependent adenovirus (HDAd), has many notable characteristics as a gene delivery vector for this particular type of gene therapy, including broad tropism, high infectivity, a large transgene cargo capacity, and an absence of integration into the host genome. Additionally, GLAd ensures long-term transgene expression in host organisms owing to its minimal immunogenicity, since it was constructed following the deletion of all the genes from an adenovirus. However, the clinical use of GLAd for the treatment of inherited genetic diseases has been hampered by unavoidable contamination of the highly immunogenic adenovirus used as a helper for GLAd production. Here, we report the production of GLAd in the absence of a helper adenovirus, which was achieved with a helper plasmid instead. Utilizing this helper plasmid, we successfully produced large quantities of recombinant GLAd. Importantly, our helper plasmid-based system exclusively produced recombinant GLAd with no generation of helper plasmid-originating adenovirus and replication-competent adenovirus (RCA). The recombinant GLAd that was produced efficiently delivered transgenes regardless of their size and exhibited therapeutic potential for Huntington’s disease (HD) and Duchenne muscular dystrophy (DMD). Our data indicate that our helper plasmid-based GLAd production system could become a new platform for GLAd-based gene therapy.
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Bates, Emily A., John R. Counsell, Sophie Alizert, Alexander T. Baker, Natalie Suff, Ashley Boyle, Angela C. Bradshaw, et al. "In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications." Viruses 13, no. 8 (July 28, 2021): 1483. http://dx.doi.org/10.3390/v13081483.
Full textAbstract:
The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile—remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications.
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Reddy, Vijay S., Xiaodi Yu, and Michael A. Barry. "Refined Capsid Structure of Human Adenovirus D26 at 3.4 Å Resolution." Viruses 14, no. 2 (February 17, 2022): 414. http://dx.doi.org/10.3390/v14020414.
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Various adenoviruses are being used as viral vectors for the generation of vaccines against chronic and emerging diseases (e.g., AIDS, COVID-19). Here, we report the improved capsid structure for one of these vectors, human adenovirus D26 (HAdV-D26), at 3.4 Å resolution, by reprocessing the previous cryo-electron microscopy dataset and obtaining a refined model. In addition to overall improvements in the model, the highlights of the structure include (1) locating a segment of the processed peptide of VIII that was previously believed to be released from the mature virions, (2) reorientation of the helical appendage domain (APD) of IIIa situated underneath the vertex region relative to its counterpart observed in the cleavage defective (ts1) mutant of HAdV-C5 that resulted in the loss of interactions between the APD and hexon bases, and (3) the revised conformation of the cleaved N-terminal segments of pre-protein VI (pVIn), located in the hexon cavities, is highly conserved, with notable stacking interactions between the conserved His13 and Phe18 residues. Taken together, the improved model of HAdV-D26 capsid provides a better understanding of protein–protein interactions in HAdV capsids and facilitates the efforts to modify and/or design adenoviral vectors with altered properties. Last but not least, we provide some insights into clotting factors (e.g., FX and PF4) binding to AdV vectors.
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Tan, Ee Wern, Noraini Abd-Aziz, Chit Laa Poh, and Kuan Onn Tan. "Engineered Oncolytic Adenoviruses: An Emerging Approach for Cancer Therapy." Pathogens 11, no. 10 (October 4, 2022): 1146. http://dx.doi.org/10.3390/pathogens11101146.
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Cancer is among the major leading causes of mortality globally, and chemotherapy is currently one of the most effective cancer therapies. Unfortunately, chemotherapy is invariably accompanied by dose-dependent cytotoxic side effects. Recently, genetically engineered adenoviruses emerged as an alternative gene therapy approach targeting cancers. This review focuses on the characteristics of genetically modified adenovirus and oncology clinical studies using adenovirus-mediated gene therapy strategies. In addition, modulation of the tumor biology and the tumor microenvironment as well as the immunological responses associated with adenovirus-mediate cancer therapy are discussed.
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Echavarría, Marcela. "Adenoviruses in Immunocompromised Hosts." Clinical Microbiology Reviews 21, no. 4 (October 2008): 704–15. http://dx.doi.org/10.1128/cmr.00052-07.
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SUMMARY The number of patients with acquired immunodeficiency has grown steadily as a result of both a larger number of patients receiving solid organ and hematopoietic stem cell transplants and their longer survival times. The use of newer, more potent immunosuppressive regimens has increased the frequency of severe adenovirus infections. Human adenoviruses are a large group of viruses, represented by at least 52 serotypes with various genotypes divided into genomic clusters, and these may cause a broad variety of clinical manifestations. The development of molecular methods has increased the sensitivity and rapidity of adenovirus infection diagnosis. The implementation of PCR assays has significantly contributed to the identification of patients with disseminated adenovirus disease. More recently, the development of real-time PCR assays has permitted virus quantification and patient follow-up. There is no treatment for adenovirus with demonstrated efficacy, although cidofovir is widely used. Sensitive diagnostic tests for adenovirus can contribute to the early diagnosis and successful treatment of life-threatening adenovirus infections, especially in complex immunocompromised patients. The development of improved adenovirus therapy still remains a challenge. Adenovirus genetic diversity should be considered for diagnosis, typing, and therapeutic interventions.
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Athukorala, Ajani, Karla J. Helbig, Brian P. Mcsharry, Jade K. Forwood, and Subir Sarker. "Adenoviruses in Avian Hosts: Recent Discoveries Shed New Light on Adenovirus Diversity and Evolution." Viruses 14, no. 8 (August 13, 2022): 1767. http://dx.doi.org/10.3390/v14081767.
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While adenoviruses cause infections in a wide range of vertebrates, members of the genus Atadenovirus, Siadenovirus, and Aviadenovirus predominantly infect avian hosts. Several recent studies on avian adenoviruses have encouraged us to re-visit previously proposed adenovirus evolutionary concepts. Complete genomes and partial DNA polymerase sequences of avian adenoviruses were extracted from NCBI and analysed using various software. Genomic analyses and constructed phylogenetic trees identified the atadenovirus origin from an Australian native passerine bird in contrast to the previously established reptilian origin. In addition, we demonstrated that the theories on higher AT content in atadenoviruses are no longer accurate and cannot be considered as a species demarcation criterion for the genus Atadenovirus. Phylogenetic reconstruction further emphasised the need to reconsider siadenovirus origin, and we recommend extended studies on avian adenoviruses in wild birds to provide finer evolutionary resolution.
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Stercz, Balázs, Károly Nagy, and József Ongrádi. "Adenovirus infections in immuncompromised patients." Orvosi Hetilap 153, no. 48 (December 2012): 1896–904. http://dx.doi.org/10.1556/oh.2012.29496.
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Human adenoviruses function as genetic models and vectors for gene therapy. Upper respiratory, gastrointestinal or ocular infections usually have mild course without any major complication in immuncompetent individuals. However, reactivation from latency in immuncompromised patients may lead to death. Depending on the underlying diseases, different adenovirus serotypes damage different organs. In children with severe combined immunodeficiency syndrome, serotypes of species A and C induce lung, liver or bladder inflammation. Paediatric hematopoietic stem cell transplantation is frequently followed by serotype 31-induced pneumonia, enteritis, cystitis. B serotypes can destroy transplanted organs. In AIDS patients, D and novel F serotypes cause enteritis. Recombinants of B serotypes induce urinary tract infections. Progression of lymphomas, tumours, and systemic lupus erythematosus might be facilitated by immunsuppressive effects of adenoviruses. As far as the diagnostic work-up of adenoviruses, detection of viral DNA and virus copy number is predictive, while serology testing is quite unrealiable. For treatment, cidofovir derivates, ribavirin, ganciclovir, vidarabine and microRNA have been used. Orv. Hetil., 2012, 153, 1896–1904.
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Weinberg, Adriana, Maria Cristina D. S. Fink, Sueko Takimoto, Maria Akiko Ishida, and Maria Cândida O. Souza. "Enzyme linked immunosorbent assay: determination of anti-adenovirus antibodies in an infant population." Revista do Instituto de Medicina Tropical de São Paulo 31, no. 5 (October 1989): 336–40. http://dx.doi.org/10.1590/s0036-46651989000500007.
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In order to define an accurate assay for anti-adenovirus antibody detection, a recently developed ELISA was compared with IFA and CF. On 58 sera, the ELISA was more sensitive than both CF and IFA, which showed relative sensitivities of 63% and 94%, respectively. It was not possible to determine the exact specificity of the tests because of the lack of a gold standard. Furthermore, the ELISA was used to define the prevalence of adenovirus antibodies in 116 infants between 1 and 24 months old (mean 7.28). The data showed that maternal antibodies waned by the age of 5 to 6 months and that more than 80% of the children had been infected by adenoviruses by the age of 10 months.
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Thwiny, Hazim Talib, Nawar Jasim Alsalih, Zeayd Fadhil Saeed, Ali Mosa Rashid Al-Yasari, Moyed Abd AlHussein Al-Saadawe, and Mohenned Abd ElHussein Alsaadawi. "Prevalence and seasonal pattern of enteric viruses among hospitalized children with acute gastroenteritis in Samawah, Iraq." Journal of Medicine and Life 15, no. 1 (January 2022): 52–57. http://dx.doi.org/10.25122/jml-2021-0158.
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Almost all of the deaths happening under the age of 5 occur in the developed countries of Africa and Asia. This study included children admitted to the surgical care, aged 6 months to 5 years, who suffered from acute gastroenteritis and received treatment at Samawah, Iraq, from December 2018 to December 2019. Test results detected different types of rotaviruses, adenoviruses, astroviruses using ELISA. 56.6% of the infections were attributed to a viral pathogen. The main cause was attributed to rotavirus and adenovirus. The causative agents of diarrheal diseases in 28.1% of cases are rotaviruses, in 17.05% – adenoviruses, in 11.43% – astroviruses. Viral mono-infections are detected more often than mixed infections. Viral intestinal infections are characterized by seasonality and rise in the cold season, with a peak incidence of rotavirus infection in April, adenovirus infection in November, and astrovirus infection in December.
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Sakurai, Fuminori, Masashi Tachibana, and Hiroyuki Mizuguchi. "Adenovirus vector-based vaccine for infectious diseases." Drug Metabolism and Pharmacokinetics 42 (February 2022): 100432. http://dx.doi.org/10.1016/j.dmpk.2021.100432.
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Ilan, Yaron, Hidetsugu Saito, Narsing Thummala, and Namita Chowdhury. "Adenovirus-mediated Gene Therapy of Liver Diseases." Seminars in Liver Disease 19, no. 01 (1999): 49–59. http://dx.doi.org/10.1055/s-2007-1007097.
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Hashemzadeh, Mohammad S. "Investigating the Role of Adenovirus, Herpes Simplex 1, 2, and Varicella Zoster Virus in Incidence of Conjunctivitis in Tehran, Iran." Romanian Journal of Military Medicine 126, no. 1 (January 2, 2023): 53–57. http://dx.doi.org/10.55453/rjmm.2023.126.1.9.
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"Conjunctivitis is one of the most common ocular diseases across the world. In this study, the prevalence of viral Conjunctivitis in patients who were referred to the Eye specialized Hospitals was evaluated. Some of the most important viruses that cause conjunctivitis are Human Adenoviruses (HAdV), Herpes Simplex 1, 2 (HSV-1, HSV-2), and Varicella Zoster Virus (VZV). The clinical diagnosis of eye viral infections is difficult and often controversial. Thus, research to experiment with these causative factors is of pivotal importance. In this cross-sectional study, 200 conjunctival swab samples were collected from symptomatic patients with signs of conjunctivitis who had been referred to two hospitals. After DNA extraction, Multiplex Real-Time PCR was carried out in two separate reactions for each sample. Among 200 collected samples, 34 (17%) and 8 (4%) were positive for Adenovirus and HSV-1 DNA, respectively. There were no HSV-2 and VZV conjunctivitis. No significant correlation was identified between gender and conjunctivitis (P-value: 0.845); however, there was a close correlation between age and conjunctivitis (Pvalue: 0.05). In this study, 66.3% of Adenoviral conjunctivitis occurs in the summer compared to 33.7% in spring. No significant seasonal variation was observed for HSV-1. Our results showed that adenovirus has a key role in causing viral conjunctivitis. "
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Lenaerts, L., E. Verbeken, E. De Clercq, and L. Naesens. "Mouse Adenovirus Type 1 Infection in SCID Mice: an Experimental Model for Antiviral Therapy of Systemic Adenovirus Infections." Antimicrobial Agents and Chemotherapy 49, no. 11 (November 2005): 4689–99. http://dx.doi.org/10.1128/aac.49.11.4689-4699.2005.
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ABSTRACT The importance of human adenovirus infections in immunocompromised patients urges for new and adequate antiadenovirus compounds. Since human adenoviruses are species specific, animal models for systemic adenovirus infections rely on a nonhuman adenovirus. We established mouse adenovirus type 1 (MAV-1) infection of BALB/c SCID mice as a model for the evaluation of antiadenovirus therapy. In vitro studies with mouse embryonic fibroblasts pointed to the acyclic nucleoside phosphonate cidofovir and the N-7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242) as markedly active compounds against MAV-1. SCID mice, infected intranasally with MAV-1, developed a fatal disseminated infection after approximately 19 days, characterized by hemorrhagic enteritis. Several techniques were optimized to monitor viral, immunological, and pathological aspects of MAV-1 infection. Real-time PCR quantification of viral DNA revealed that after replication in the lungs, virus disseminated to several organs, including the brain, liver, spleen, intestine, heart, and kidneys (resulting in viruria). Immunohistochemical staining showed that MAV-1 was localized in the endothelial cells of the affected organs. Using reverse transcription-PCR, tissue levels of proinflammatory cytokines (i.e., interleukin-1β and tumor necrosis factor alpha) were found to be markedly increased. The MAV-1/SCID model appears to be an appropriate model for in vivo evaluation of antiadenovirus agents. Treatment with cidofovir or S-2242 at a dose of 100 mg per kg of body weight resulted in a significant delay in MAV-1-related death, although these antivirals were unable to completely suppress virus replication despite continued drug treatment. These findings suggest that complete virus clearance during antiviral therapy for disseminated adenovirus infection may require an efficient adaptive immune response from the host.
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Piatti, Gabriella. "Pre-Transplant Screening for Latent Adenovirus in Donors and Recipients." Open Microbiology Journal 10, no. 1 (February 2, 2016): 4–11. http://dx.doi.org/10.2174/1874285801610010004.
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Human adenoviruses are frequent cause of slight self-limiting infections in immune competent subjects, while causing life-threatening and disseminated diseases in immunocompromised patients, particularly in the subjects affected by acquired immunodeficiency syndrome and in bone marrow and organ transplant recipients. Here, infections interest lungs, liver, encephalon, heart, kidney and gastro enteric tract. To date, human adenoviruses comprise 51 serotypes grouped into seven species, among which species C especially possesses the capability to persist in infected tissues. From numerous works, it emerges that in the recipient, because of loss of immune-competence, both primary infection, via the graft or from the environment, and reactivated endogenous viruses can be responsible for transplantation related adenovirus disease. The transplants management should include the evaluation of anti-adenovirus pre-transplant screening similar to that concerning cytomegalovirus. The serological screening on cytomegalovirus immunity is currently performed to prevent viral reactivation from grafts and recipient, the viral spread and dissemination to different organs and apparatus, and potentially lethal outcome.